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Lee, Seungwon,Kim, Hyekang,You, Gihoon,Kim, Young-Min,Lee, Seunghun,Le, Viet-Hoan,Kwon, Ohseop,Im, Sin-Hyeog,Kim, You-Me,Kim, Kwang Soon,Sung, Young Chul,Kim, Ki Hean,Surh, Charles D.,Park, Yunji,Lee, American Society of Hematology 2019 Blood Vol.134 No.16
<B>Abstract</B><P>Lee and colleagues investigated the role of the intestinal microbiota in steady-state hematopoieisis, demonstrating that microbiota-derived DNA circulates to the bone marrow, where uptake by mononuclear cells leads to inflammatory cytokine production favoring myeloid-cell maturation of hematopoietic progenitors.</P>
Lee, Ahwon,Kang, Jun,Lee, Hyoungnam,Lee, Youn Soo,Choi, Youn Jin,Lee, Keun Ho,Nistala, Goutam J,Scafe, Charles R.,Choi, Jongpill,Yoo, Jaeeun,Han M.D, Eunhee,Kim, Yonggoo,Kim, Myungshin Elsevier 2019 Pathology, research and practice Vol.215 No.11
<P><B>Abstract</B></P> <P><B>Introduction</B></P> <P>The detection of <I>BRCA1/2</I> mutations is important because PARP1 inhibitors are approved for germline and/or somatic <I>BRCA</I>-mutated advanced ovarian cancer. Next-generation sequencing (NGS) is increasingly used in clinical practice for <I>BRCA1</I>/2 mutations. The purpose of this study was to consider several conditions of NGS <I>BRCA1/2</I> assay applicable to clinical laboratory tests, in particular for using formalin fixed paraffin embedded (FFPE) ovarian tissues.</P> <P><B>Materials and methods</B></P> <P>We selected 64 ovarian cancer patients and performed Oncomine™ BRCA assay using FFPE tissue. Effect of FFPE sample quality was analyzed by NGS quality parameters including deamination metric. Somatic variants were selected by removing germline variants of peripheral blood and interpreted as pathogenic, variants of unknown significance, and false positive.</P> <P><B>Results</B></P> <P>We found a positive relationship between the number of variants over the deamination metric and FFPE age (<I>P</I> < 0.001) with a cutoff values of approximately 0.7 and 60 months, respectively. When comparing NGS results with Sanger sequencing, NGS misreported 3 of 15 variants using default parameters which were corrected after changing parameters. We detected somatic variants in eight patients and classified them into pathogenic (n = 3), VUS (n = 3) and false positive (n = 2).</P> <P><B>Conclusions</B></P> <P>This study is important for improving <I>BRCA1/2</I> mutation detection capabilities of NGS analytical pipelines and strategy to overcome their limitations using FFPE tissue in ovarian cancer patients.</P>
Blue-Shifting Intramolecular Charge Transfer Emission by Nonlocal Effect of Hyperbolic Metamaterials
Lee, Kwang Jin,Lee, Yeon Ui,Fages, Fré,dé,ric,Ribierre, Jean-Charles,Wu, Jeong Weon,D’Alé,o, Anthony American Chemical Society 2018 NANO LETTERS Vol.18 No.2
<P>Metallic nanostructures permit controlling various photophysical processes by coupling photons with plasmonic oscillation of electrons confined in the tailored nanostructures. One example is hyperbolic metamaterial (HMM) leading to an enhanced spontaneous emission rate of emitters located nearby. Noting that emission in organic molecules is from either pi-pi* or intramolecular charge-transfer (ICT) states, we address here how HMM modifies ICT emission spectral features by comparing them with a spectral shift dependent on the local polarity of the medium. The 7.0 nm blue shift is observed in ICT emission from 4-dicyanomethylene-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran dispersed into a polymer matrix prepared on HMM multilayered structure, while no spectral shift is observed in pi-pi* emission from perylene diimide. In the frame of the Lippert-Mataga formalism, the blue shift is explained by the HMM nonlocal effects resulting from 8% decrease in refractive index and 18% reduction in dielectric permittivity. This phenomenon was also shown in a hemi-curcuminoid borondifluoride dye yielding 15.0 nm blue shift. Such a capability of spectral shift control in films by HMM structure opens new prospects for engineering organic light-emitting devices.</P>
Lee, Sukmook,Chung, Junho,Ha, In Su,Yi, Kyesook,Lee, Ji Eun,Kang, Hee Gyung,Choi, Inho,Oh, Kook-Hwan,Kim, Jae Young,Surh, Charles D,Ahn, Curie Oxford University Press 2007 International immunology Vol.19 No.12
<P>Although a severe shortage of organs in transplantation can be overcome by using xenotransplantation of porcine donor organs, profound immune rejection to xenogeneic antigens remains a main obstacle. To elucidate the role of hydrogen peroxide (H(2)O(2)) on xenogeneic immune responses, we investigated its effects on porcine aortic endothelial cells (PAECs). We found that H(2)O(2) can specifically induce vascular cell adhesion molecule-1 (VCAM-1) expression on PAECs, but little on human umbilical vein endothelial cells (HUVECs) and aortic endothelial cells (HAECs). Furthermore, we further confirmed that H(2)O(2) induces activation of NFkappaB in PAECs, but not in HAECs. Interestingly, cell adhesion assay showed that U937, human promonocytic leukocyte, can adhere to PAECs in an H(2)O(2)-dependent manner and by using a neutralizing assay with anti-VCAM-1-specific antibodies, we also found that the interaction is mediated primarily by VCAM-1. Finally, we also demonstrated that up-regulation of VCAM-1 expression on PAECs by reactive oxygen species-producing HL-60, human leukemic neutrophil cells, could be significantly diminished by over-expressing an H(2)O(2)-removing catalase. In summary, our results suggest that NFkappaB-dependent porcine VCAM-1 expression by H(2)O(2) may promote interaction of human leukocyte to PAECs, and thus may play an important role on inducing xenogeneic immune responses.</P>
Lee, Charles C.,Kim, Jong Hun,Kim, Ji Seung,Oh, Yun Sil,Han, Seung Min,Yoon Park, Jung Han,Lee, Ki Won,Lee, Chang Yong MDPI AG 2017 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.18 No.7
<P>Several metabolomics of polymeric flavan-3-ols have reported that proanthocyanidins are extensively metabolized by gut microbiota. 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone (DHPV) has been reported to be the major microbial metabolite of proanthocyanidins. We demonstrated that DHPV has stronger prevention effect on tumor necrosis factor (TNF)-α-stimulated adhesion of THP-1 human monocytic cells to human umbilical vein endothelial cells compared to its potential precursors such as procyanidin A1, A2, B1 and B2, (+)catechin, (−)epicatechin and its microbial metabolites such as 3-(3,4-dihydroxyphenyl)propionic acid and 2-(3,4-dihydroxyphenyl)acetic acid. Mechanism study showed that DHPV prevents THP-1 monocyte-endothelial cell adhesion by downregulating TNF-α-stimulated expressions of the two biomarkers of atherosclerosis such as vascular cell adhesion molecule-1 and monocyte chemotactic protein-1, activation of nuclear factor kappa B transcription and phosphorylation of I kappa-B kinase and IκBα. We suggested that DHPV has higher potentiality in prevention of atherosclerosis among the proanthocyanidin metabolites.</P>
Lee, Charles C.,Dudonné,, Sté,phanie,Kim, Jong Hun,Kim, Ji Seung,Dubé,, Pascal,Kim, Jong-Eun,Desjardins, Yves,Park, Jung Han Yoon,Lee, Ki Won,Lee, Chang Yong Applied Science Publishers 2018 Food chemistry Vol.240 No.-
<P><B>Abstract</B></P> <P>Among many functional foods and their phytochemicals, ingestion of soybean (<I>Glycine max</I>) is highly correlated to reduced risk of cardiovascular diseases. Validation of potential health benefits of functional foods requires information about the bioavailability and metabolism of bioactive compounds. In this context, several phase I and II metabolites of isoflavones were target-analyzed in the plasma of rats acutely supplemented with soybean embryo extract. A daidzein metabolite, 7,8,4′-trihydroxyisoflavone (7,8,4′-THI), was found to have the highest average area under curve value (574.3±112.8). Therefore, its potential prevention effect on atherosclerosis was investigated using monocyte-endothelial cell adhesion assay. Different from its precursor daidzein or daidzin, 7,8,4′-THI attenuated adhesion of THP-1 monocytes to tumor necrosis factor-alpha (TNF-α) stimulated human umbilical vein endothelial cells (HUVECs). In addition, 7,8,4′-THI significantly downregulated TNF-α stimulated the expression of vascular cell adhesion molecule-1 and monocyte chemotactic protein-1 and phosphorylation of IκB kinase and IκBα involved in the initiation of atherosclerosis in HUVECs. Therefore, 7,8,4′-THI, a highly bioavailable hydroxylated isoflavone metabolite, has potential anti-atherosclerotic effect via inhibiting monocyte-endothelial adhesion.</P> <P><B>Highlights</B></P> <P> <UL> <LI> 7,8,4′-Trihydroxyisoflavone was found in the rat plasma after soybean intake. </LI> <LI> The highest average AUC of 7,8,4′-THI was 10 times higher than its precursor daidzein. </LI> <LI> 7,8,4′-THI inhibited TNF-α stimulated monocyte-endothelial cell adhesion. </LI> </UL> </P>